Lipids are a diverse and ubiquitous group of compounds which have many key biological functions, such as acting as structural components of cell membranes, serving as energy storage sources and participating in signaling pathways. In addition to functions such as providing cellular structure, energy storage and cellular transport, the role of lipid molecules in a variety of cell signaling pathways has also been the focus of recent research.
Lipid signaling may occur via activation of a variety of receptors, including G protein-coupled and nuclear receptors, and members of several different lipid categories have been identified as signaling molecules and cellular messengers. There are many examples of important signaling lipids including sphingosine-1-phosphate, a sphingolipid derived from ceramide that is a potent messenger molecule involved in regulating calcium mobilization, cell growth, and apoptosis, diacylglycerol and the inositol phosphates derived from the phosphatidylinositolphosphates, involved in calcium-mediated activation of protein kinase C as well as the prostaglandins, which are one type of fatty-acid derived eicosanoid involved in inflammation and immunity.
One class of molecules currently being investigated for therapeutic activity includes the sphingolipids, such as sphingosine-1-P, sphingosine, ceramide, gangliosides and sphigomyelin.
In addition to potential as a therapeutic agent in and of itself, sphingosine can be used as a starting material in the synthesis of a variety of sphingolipids, including, but not limited to, sphingosine-1-P, ceramide, gangliosides and sphigomyelin.
Current synthetic methods for the production of various sphingolipids are currently not suitable for large scale production. To realize the potential for various lipid molecules as therapeutics, it is essential that the lipid molecules be available in a highly purified form and in quantities and price points compatible for use in pharmaceutical products. Such issues also apply to certain inhibitors of sphingolipid synthesis, which are structurally related to various intermediates in sphingolipid production. Therefore, the art is lacking synthetic methods for the economical production of sphingolipids and inhibitors of sphingolipid synthesis.
The present disclosure provides a series of compounds useful in the production of sphingolipids, such as, but not limited to, sphingosine and compounds incorporating sphingosine (including, but not limited to, sphingosine-1-P, ceramide, gangliosides and sphigomyelin) as well as compounds useful as inhibitors of sphingolipid synthesis.